Eighteen children with perennial bronchial asthma with an average age of 9.6 yr were studied with respect to the protective effect of ketotifen on bronchial hyperreactivity. All children included demonstrated bronchial reversibility after inhalation of salbutamol, and the methacholine challenge produced a decrease of the forced expiratory volume during the first second of at least 20% in the concentration interval of 0.25 mg/ml to 4.0 mg/ml. The study was double-blind with patients divided into two parallel groups treated for 12 wk with ketotifen or placebo. Methacholine provocation tests were performed every fourth week during this period. No differences between the challenges before and during the treatment period were found in either group, nor were any differences found between the ketotifen and placebo groups. Long-term treatment with ketotifen does not appear to alter the bronchial hyperreactivity in children with bronchial asthma.